Dendritic cells (DCs) are specialized cells of the immune system. DCs have the unique capacity for initiating primary and secondary T and B lymphocyte responses by presenting antigens in the form of peptides bound to cell-surface major histocompatibility complex (MHC) molecules. The antigen-presentation function of dendritic cells has been correlated with the high-level expression of human dendritic and epithelial cell 205 receptor (DEC-205) (Jiang et al. (1995) Nature 375(11)151).
DEC-205 is an endocytic receptor found primarily on dendritic cells, but is also found on B cells, brain capillaries, bone marrow stroma, epithelia of intestinal villi and pulmonary airways, as well as the cortical epithelium of the thymus and the dendritic cells in the T cell areas of peripheral lymphoid organs. DEC-205 is expressed at high levels on DCs in the T cell areas of lymphoid organs (Kraal et al. (1986) J. Exp. Med. 163:981; Witmer-Pack et al. (1995) Cell. Immunol. 163:157). DEC-205 has ten membrane-external, contiguous C-type lectin domains (Id.; Mahnke et al. (2000) J. Cell Biol. 151:673) which mediate the efficient processing and presentation of antigens on MHC class II products in vivo (Hawiger et al. (2001) J. Exp. Med. 194:769). It has been shown that small amounts of injected antigen, targeted to DCs by the DEC-205 adsorptive pathway, are able to induce solid peripheral CD8+ T cell tolerance (Bonifaz et al. (2002) J. Exp. Med. 196(12):1627).
Despite recent advances in the characterization of dendritic cells, very little is known regarding dendritic cell-specific receptors, such as DEC-205, and few reagents are available which are specific to dendritic cells. Reagents, in particular antibodies, which react specifically or preferentially with dendritic cells, such as through DEC-205, have great potential as targeting agents to induce potent immune responses to tumor or infectious disease antigens. These cell-specific targeting agents could also be engineered to deliver toxins to eliminate potent antigen presenting cells (e.g., dendritic cells) in bone marrow and organ transplantations or other autoimmune disorders. Accordingly, such dendritic cell-specific binding agents possess great therapeutic and diagnostic value.